1. Field of the Invention
The present invention generally relates to a composition for treating hearing loss. More specifically, the present invention relates to a composition for treating hearing loss that includes components that function through different biological mechanisms and provide an additive effect that is equal to or greater than a sum of the effects of the individual components, and a method of treating hearing loss including the step of administering the composition to a mammal prior to or within 3 days following trauma to the inner ear.
2. Description of the Related Art
Extensive studies have been performed on compositions for treating hearing loss, along with methods of treating hearing loss using various compositions. In particular, antioxidants, among numerous other components, have been found to play a role in the prevention of noise-induced hearing loss. Specific antioxidants shown to be partially effective in reducing noise-induced hearing loss in animal models include glutathione (GSH)/glutathione monoethyl ester, N-acetylcysteine (NAC), resveratrol, allopurinol, R-phenylisopropyladenosine, and vitamins A, C, and E. Otoprotective effects of the above individual dietary antioxidants are well known in the art.
In addition to antioxidants, many other components have separately been investigated and found to be somewhat efficacious in treating hearing loss. Vasodilators are one class of components that have proven moderately useful for preventing hearing loss. It is known in the art that high levels of noise result in a decrease in blood flow to the inner ear, although the mechanism underlying this noise induced decrease has not been clear until very recently. On the basis of the observed decrease, it has long been speculated that this decrease in blood flow may lead to cell death in sensitive hair cells within a cochlea of the ear and accordingly an increase in blood flow may protect the inner ear cells from noise-induced death. Some vasodilators promote increased blood flow to the inner ear and, thus, help to protect the inner ear from trauma as a result of high levels of noise. Specific examples of vasodilators proven to partially prevent hearing loss include magnesium, betahistine, and hydroxyethyl starch (HES).
To date, little, if any, additive effects have been found to exist by combining many of the known components for treating hearing loss. Additive effects, as used herein, refer to effects that are equal to or greater than a sum of the effects of the individual components. For the most part, no greater effect is observed by combining many of the different components that are effective in treating hearing loss than the effect of the most effective individual component in the composition, i.e., combinations of agents are only as effective as the most effective single agent delivered alone. For example, FIG. 1 shows the results of experimentation relative to additive effects of Trolox®, which is a water-soluble analogue of alpha-tocopheral (vitamin E), and betahistine. The experimental conditions are described in further detail in the Examples section below. As is evident from FIG. 1, the combined effect of Trolox® and betahistine in minimizing threshold shift, which correlates to hearing loss, is no greater than the effect of the most effective of either Trolox® or betahistine alone for any given experiment. As such, the combination of Trolox® and betahistine does not produce an additive effect in treating hearing loss.
As the understanding of the mechanisms by which the various antioxidants work to treat or prevent hearing loss has become clearer, it has been found that combinations of certain antioxidants that act via complementary, but different, biochemical mechanisms may be more effective than the individual antioxidants alone. However, given the volume and variety of components that are known to affect hearing loss, as well as lack of knowledge relative to specific mechanisms by which the components function, additive effects between components have not been recognized to date.
In spite of the fact that additive effects between various components have not been recognized to date, certain disclosures have been made that generally group together all known components for treating hearing loss. These disclosures do not teach with sufficient specificity combinations of specific components that exhibit additive effects in treating hearing loss. For example, U.S. Pat. No. 6,093,417 is directed to a composition to treat ear disorders. The composition is topically applied into an ear canal to treat the hearing disorder. Although the U.S. Pat. No. 6,093,417 is directed to a composition that may include many components that are known to be somewhat effective in reducing hearing loss alone, including vitamins A, C, and E along with vasodilators and magnesium salts, there is no recognition of an additive effect between any of the components. As is evident from the above description relative to FIG. 1, many combinations of components do not exhibit additive effects. As such, the random combination of agents disclosed in the U.S. Pat. No. 6,093,417 would not necessarily be expected to provide any greater effect for treating hearing loss if included in the composition. Furthermore, effectiveness of the individual components greatly varies between oral, intravenous, and topical administration, and compositions for treating hearing loss are formulated differently depending on the contemplated mode of administration. Finally, the U.S. Pat. No. 6,093,417 does not teach with sufficient specificity biologically effective amounts of each component that would be sufficient to produce an effect individually, let alone additive effects between the various components. Thus, the disclosure of the U.S. Pat. No. 6,093,417 provides no further teaching than what was already known about each of the components, i.e., that each component, when used individually, is modestly effective in preventing hearing loss.
Although many of the components that are used to treat or prevent hearing loss provide other beneficial functions and are included in multivitamins, known multivitamins do not include biologically effective amounts of the components sufficient to treat or prevent hearing loss. Furthermore, multivitamins are generally used as part of a regular dietary regimen and there is no data that suggests the use of multivitamins that include a specific combination and concentration of components to prevent hearing loss induced by noise or other stress.
The use of dietary antioxidants to prevent visual dysfunction is disclosed in U.S. Pat. No. 6,660,297. The U.S. Pat. No. 6,660,297 specifically discloses vitamins A, C, and E in amounts that may be biologically effective to treat or prevent hearing loss. However, a combination of vitamins A, C, and E alone is not sufficient to yield clinically significant protection against noise induced hearing loss and the addition of zinc and copper as disclosed in the U.S. Pat. No. 6,660,297 would not be expected to reduce hearing loss. Furthermore, there is no suggestion or teaching in the U.S. Pat. No. 6,660,297 to use the composition for anything other than treating visual dysfunction.
Thus, there is an opportunity to provide a composition and a method of treating hearing loss including the step of administering the composition that includes a specific combination of components having an additive effect that is equal to or greater than the sum of the effect of the individual components in treating hearing loss when used in biologically effective amounts.